Studies of dietary obesity in experimental animals have been described which may provide clues to treating human obesity. The first series of studies will explore the differences between two strains of rodents one of which (Osborne-Mendel) becomes fat eating a high fat diet, and the other one of which (S 5B/P1) does not become obese under the same conditions. Several possible sites exist at which this difference in response to a high fat diet might occur. The first is a difference in taste, the second is a difference in feedback effects of nutrients introduced into the gastro-intestinal tract; the third is a post-ingestional effect of foods mediated through the nutrients themselves; the fourth involves neurohumoral and/or hormoral mechanisms; the fifth involves changes in the permeability of the blood brain barrier to glucose or ketones; and the sixth involves differences in dietary thermogenesis and activity of brown adipose tissue. Each of these possibilities will be examined systematically. The second series of experiments are designed to explore the basis for the fact that rats fed a high diet containing long chain triglycerides will become obese. Whereas rats fed the medium chain triglycerides do not. One hypothesis which underlies part of this study is that rapid fatty acid oxidation which results from the absorption of medium chain fatty acids, and which occurs to a much smaller degree when the diet contains long chain fatty acids, reduces food intake either directly or indirectly. The second hypothesis to be tested is that these fats have different effects on transport of ketones into the brain.